Persistence is a transient and non-inheritable tolerance to antibiotics by a small fraction of a bacterial population. One of the proposed determinants of bacterial persistence is toxin–antitoxin systems (TASs) which are also implicated in a wide range of stress-related phenomena. Maisonneuve E, Castro-Camargo M, Gerdes K. 2013. Cell 154:1140–1150 reported an interesting link between ppGpp mediated stringent response, TAS, and persistence. It is proposed that accumulation of ppGpp enhances the accumulation of inorganic polyphosphate which modulates Lon protease to degrade antitoxins. The decrease in the concentration of antitoxins supposedly activated the toxin to increase in the number of persisters during antibiotic treatment. In this study, we show that inorganic polyphosphate is not required for transcriptional activation of yefM/yoeB TAS, which is an indirect indication of Lon-dependent degradation of YefM antitoxin. The Δ10 strain, an Escherichia coli MG1655 derivative in which the 10 TAS are deleted, is more sensitive to ciprofloxacin compared to wild type MG1655. Furthermore, we show that the Δ10 strain has relatively lower fitness compared to the wild type and hence, we argue that the persistence related implications based on Δ10 strain are void. We conclude that the transcriptional regulation and endoribonuclease activity of YefM/YoeB TAS is independent of ppGpp and inorganic polyphosphate. Therefore, we urge for thorough inspection and debate on the link between chromosomal endoribonuclease TAS and persistence.

35Persistence is a transient and non-inheritable tolerance to antibiotics by a small fraction of a 36 bacterial population. One of the proposed determinants of bacterial persistence is Toxin- Ciprofloxacin and Ampicillin as well as has lowered fitness. This is likely because of the 63 polar effects on the adjacent genes caused by the genetic manipulation of multiple TAS loci.

Toxin-antitoxins systems (TAS) are prokaryotic operons containing two small overlapping genes which encode two components referred to as toxin and antitoxin. Involvement of TAS in bacterial programmed cell death (PCD) is highly controversial. MazEF, a typical type II TAS, is particularly implicated in mediating PCD in Escherichia coli. Hence, we compared the metabolic fitness and stress tolerance of E. coli strains (MC4100 and its mazEF-derivative) which were extensively used by proponents of mazEF-mediated PCD. We found that both the strains are deficient in relA gene and that the ΔmazEF strain has lower fitness and stress tolerance compared to wild type MC4100. We could not reproduce mazEF mediated PCD which emphasizes the need for skeptic approach to the PCD hypothesis.

Toxin-antitoxins systems (TAS) are prokaryotic operons containing two small overlapping genes which encode two components referred to as Toxin and Antitoxin. Involvement of TAS in bacterial programmed cell death (PCD) is highly controversial. MazEF, a typical type II TAS, is particularly implicated in mediating PCD in Escherichia coli. Hence, we compared the metabolic fitness and stress tolerance of E. coli strains (MC4100 and its mazEF -derivative) which were extensively used by proponents of mazEF-mediated PCD. We found that both the strains are deficient in relA gene and that the Δ mazEF strain has lower fitness and stress tolerance compared to wild type MC4100. Furthermore, these strains are likely not isogenic. We could not reproduce mazEF mediated PCD which emphasizes the need for skeptic approach to the PCD hypothesis.

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